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The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.
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Animales , Ratas , Interleucina-6 , Farmacología en Red , Experimentación Animal , Factor de Necrosis Tumoral alfa , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Cirrosis Hepática/genética , Medicina Tradicional China , Cápsulas , Fosfatidilinositol 3-Quinasa Clase I , Colágeno , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Superior labrum anterior posterior (SLAP) injury is a major challenge for orthopedic surgeons, due to the poor healing ability of the injured labrum. Although arthroscopic surgery is the gold standard for the treatment of SLAP injury, there are still disputes about the adaptation of different surgical techniques, the choice of anchors during operation, knotted or knotless anchors, and fixation methods. The authors believe that arthroscopic repair of SLAP lesions is effective for young patients with intact glenoid labrum(<35 years old) or with extensive activity, where single and knotless anchor is preferred. For the older patients(≥35 years old) with degeneration and wear of glenoid labrum, biceps tenodesis is more preferable, and interference screw fixation technique is recommended. As for patients with failed SLAP repair, biceps tenodesis can achieve a high success rate as a revision surgery. By review of the relevant literature in recent years, this paper summarizes the adaptation of different surgical methods of arthroscopic treatment of SLAP injury, intraoperative anchoring techniques, fixation methods and other improved surgical techniques.
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Humanos , Adulto , Articulación del Hombro/cirugía , Artroscopía/métodos , Traumatismos de los Tendones/cirugía , Lesiones del Hombro/cirugía , Tenodesis/métodosRESUMEN
Due to the complexity of tumor pathology, the demand for the combined use of multiple drugs in clinical treatment has become increasingly clear-cut. Multi-drug combination can act on multiple pathways and multiple targets simultaneously to exert synergistic effects. However, the current delivery strategy for multi-drug combination still needs to be optimized. Nano-drug delivery systems can carry drugs to overcome physiological and pathological barrier to target tumor tissues and cells, achieve the goal of continuous, controllable, and targeted delivery, and enhance the efficacy of anti-tumor synergism and detoxification. To meet the new requirements for smarter and more accurate antitumor multi-drug combinational therapy, the nano-drug delivery system has been well-designed to realize more functions. For instance, delivery of multiple drugs in accurate proportions and doses can make the multi-drug synergistic effect more precise; stimulus-responsive drug release can improve selectivity and reduce side effects; controlling the time-course relationship of multiple drugs can realize sequential drug combination effect. It has shown broad prospects in the field of tumor multidrug therapy and has become one of the new directions of research and development. This article reviews the recent developments in the application of tumor drug combination therapy strategies and their delivery systems, and analyzes the new requirements and challenges of multidrug combination for the development of nano-drug delivery systems.
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Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.
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The surgical treatment of massive rotator cuff tears is a clinical challenge for orthopaedic surgeons. Moreover, tendon retraction, adhesions and fatty infiltration after rotator cuff tear will further increase the difficulty of surgical repair. Therefore, it has become a hotspot and difficulty to repair massive rotator cuff tears with a better way in current research. In recent years, with the continuous development of arthroscopic techniques, shoulder arthroscopic surgery has become the gold standard for the treatment of massive rotator cuff tears, but the adaptations, effects and combined application of different surgical methods are still controversial. The author believes that arthroscopic debridement of shoulder joint and acromioplasty or tuberoplasty could relieve shoulder pain in the short-term for elderly patients with lower functional requirements;long biceps tenotomy or tenodesis is effective for patients with biceps long head tendon injury; complete repair is still the first line treatment for massive rotator cuff tears, but partial repair is possible for massive rotator cuff tears that could not be completely repaired;patch augmentation technology could bring good results for young patients with high functional requirements;for patients with limited internal and external rotation of the shoulder joint and high functional requirements, tendon transfers surgery is recommended;superior capsular reconstruction is more advantageous for young patients with no obvious glenohumeral arthritis, better deltoid muscle strength and higher functional requirements. In addition, subacromial spacer implantation has become a current research hotspot due to its advantages of small trauma, low cost and relative safety, and its long-term effect still needs to be further confirmed.
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Humanos , Anciano , Lesiones del Manguito de los Rotadores/cirugía , Artroscopía/métodos , Tendones , Músculo Esquelético/cirugía , Traumatismos de los Tendones/cirugía , Resultado del TratamientoRESUMEN
Recurrent anterior dislocation of shoulder with bone defect is one of the common diseases of shoulder joint. How to effectively repair glenoid bone defect and reduce recurrence rate of shoulder dislocation is a problem that clinicians focus on. Bone grafting could stimulate bone, promote bone regeneration and bone remodeling, and restore the normal anatomical structure of glenoid. Among them, Bristow-Latarjet procedure is a classic operation for recurrent shoulder dislocation. Latarjet procedure could repair larger glenoid bone defects, but with higher surgical skills for surgeons;autogenous iliac grafting is the first choice for revision once Latarjet procedure failed;osteochondral grafting (autogenous and allogenous) has certain advantages in reconstructing original articular surface and preventing joint degeneration, but autologous osteochondral grafting may cause secondary injury, while immune rejection is difficult to avoid for allogenous osteochondral grafting. With the improvement of composite materials, and the mechanism of bone regeneration and remodeling, as well as the advantages and disadvantages of bone grafting, tissue engineering technology may become an effective method for the treatment of glenoid bone defect in the future.
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Humanos , Trasplante Óseo , Inestabilidad de la Articulación , Recurrencia , Hombro , Luxación del Hombro/cirugía , Articulación del HombroRESUMEN
BACKGROUND@#Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.@*METHODS@#A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test.@*RESULTS@#The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = -5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t = -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).@*CONCLUSION@#EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.
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Anciano , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Quimiocinas CXC/efectos de los fármacos , Delirio , Método Doble Ciego , Edaravona , Ligandos , Complicaciones PosoperatoriasRESUMEN
Shoulder arthroscopic as a conventional method usually is applied to repair rotator cuff tears. In clinical, plenty single-row, double-row and transosseous tunnels suture technique are performed, but the ideal suture technique for rotator cuff repair is not found. Compared with single-row, double-row has better strength in biomechanics property. As the two best suture technique among the single-row, massive cuff stitch and modified Mason-Allen suture have the strongest biomechanics property. Clinical trials indicate that double-row could improve healing rates, but there are no significant difference in clinical outcome functional scores. Transosseous tunnel techniques possess a better bio-mechanic property, which could improve regional micro-environment and induce tendon-bone healing. Transosseous tunnel techniques are better for small to media size rotator cuff tears and osteoporosis patient. The author suggest that optimal rotator cuff repair technique should performed according to skill of performer and individual of patient by analysing bio-mechanic properties, clinical outcome, operative complexity and patient situation. The technique should follow simple opertaion, rapid, less trauma, stable fixation and utility to perform.
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Humanos , Artroscopía , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/cirugía , Anclas para Sutura , Técnicas de Sutura , SuturasRESUMEN
The surgical treatment of recurrent anterior shoulder dislocation is a difficult problem in the field of sports injury medicine. The main reason focus on dynamic and osseous constraints of shoulder joint could not recover well. At present, arthroscopic surgery is used at home and abroad, and could receive statisfied postoperative effect, but the choice of specific surgical methods is still controversial. According to presence and size of glenoid and humeral skull defects, different treatments should be selected in clinic. The author recommends that no articular glenoid defect or glenoid defect 40% or Bristow-Latarjet if the surgical repair fails, bone grafting is used. In addition, if (humeral avulsion of glenohumeral ligaments, HAGL) injury existed, HAGL injury repair should be used. In addition to considering the important factor of bone defects, it is necessary to combine patient's age, exercise level and surgeon's technique to comprehensively select the bestsurgical method.
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Humanos , Artroscopía , Inestabilidad de la Articulación , Recurrencia , Escápula , Luxación del Hombro/cirugía , Articulación del HombroRESUMEN
OBJECTIVE@#The effects of different tube currents and voltages on image quality and radiation dose were studied to provide a theoretical basis for low-dose cone beam computed tomography (CBCT) scanning in children.@*METHODS@#Different tube currents and voltages were used to scan the incisor area of fresh Bama pig heads by CBCT. The radiation dose was recorded, and image quality was evaluated.@*RESULTS@#As the tube current or voltage decreased, the radiation dose and image quality gradually decreased. The computed tomographic dose index (CTDIvol) of 90 kV, 2.5 mA and 60 kV, 7.0 mA were all 1.7 mGy. The image quality score of the former was higher than that of the latter, and the difference between them was statistically significant (P<0.05).@*CONCLUSIONS@#Low-dose CBCT scanning appears to be able to reduce the necessary tube current during imaging by improving image quality.
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Animales , Niño , Humanos , Tomografía Computarizada de Haz Cónico , Estudios de Factibilidad , Cabeza , Dosis de Radiación , PorcinosRESUMEN
Rotator cuff repair is a common treatment for rotator cuff tear, which could effectively relieve shoulder pain and improve shoulder movement, and the incidence of rotator cuff retear after rotator cuff repair is still high. The main reason is poor tendon-bone healing in rotator cuff enthesis after rotator cuff repair and could not recover the original histological structure and biomechanical properties. Therefore, the key to solve the problem is how to effectively improve the healing of tendon bone at the end of rotator cuff. With the in-depth study of rotator cuff enthesis, various treatments have made great progress on improving tendon to bone healing of rotator cuff. Our study will discuss the researchprogress on tendon to bone healing of rotator cuff in recent years from three following aspects to provide some guidance for the clinical treatment of rotator cuff tear:the factors affecting the tendon to bone healing of rotator cuff, the recovery of tendon to bone interface promoting the tendon to bone healing of rotator cuff and the application of tissue engineering in tendon to bone healing.
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Humanos , Artroplastia , Manguito de los Rotadores , Cirugía General , Lesiones del Manguito de los Rotadores , Cirugía General , Tendones , Cirugía General , Cicatrización de HeridasRESUMEN
The rate of rotator cuff injury repair and retear is high in elderly patients due to the combination of different degrees of osteoporosis. To solve this problem, many surgeons try to reduce retear rate of rotator cuff injuries in these patients by increasing the initial fixation strength of anchors and changing local bone conditions. The rapid advances of tissue engineering have made it possible to use growth factors as an aid. However, repair of rotator cuff injury with osteoporosis is still a great challenge for clinical workers. How to better increase anchor fixation strength, improve micro-environment of tendon and bone healing, reduce the rotator cuff retear rate have become the research focus in recent years. The paper reviewed literatures on the relationshipbetween osteoporosis and rotator cuff injury, effect of osteoporosis in rotator cuff tendon healing, methods of reducing osteoporosis on rotator cuff tendon healing, in order to guide clinical treatment, improve operative effect and postoperative satisfaction.
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Anciano , Humanos , Artroplastia , Osteoporosis , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/cirugía , Tendones/cirugíaRESUMEN
Titanium alloy has good biological properties and is commonly used in orthopedics, but its bone integrity and antibacterial properties are poor, so surface modification is needed to make up for its shortcomings. Chitosan has good biocompatibility and film forming ability, and can be used as a carrier to introduce the target drug to the surface of titanium alloy, which can effectively improve the biological properties of titanium alloy materials and increase its application range. In this paper, the related research of chitosan surface modified titanium alloy materials in recent years is summarized. The modification methods of chitosan coating, the improvement of osteogenesisand antibacterial properties of titanium alloy materials are discussed in order to provide guidance for the clinical application of coating modification of titanium alloy materials.
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Aleaciones , Antibacterianos/farmacología , Quitosano , Ortopedia , Propiedades de Superficie , TitanioRESUMEN
Lateral lymph node metastasis is a common problem in the diagnosis and treatment of patients with low rectal cancer. Eastern and western scholars are still controversial about the combination of lateral lymph node dissection in TME surgery for middle and low rectal cancer.The study of correlation between laparoscopic or robotassisted lateral lymph node dissection and open surgery is still in retrospective analysis, and prospective cohort studies are needed to further confirm their superiority. Whether neoadjuvant radiochemotherapy can replace lateral lymph node dissection is still inconclusive, and it is related to the cognition that the lateral lymph node metastasis belongs to the regional or the systemic metastasis of the oriental and occidental scholars.
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OBJECTIVE: To compare the clinical outcomes of endoscopic intestinal stenting combined with elective surgery and emergency surgery at the same time for resectable left colon cancer or rectal cancer with intestinal obstruction and to explore the best time for reoperation after stent implantation. METHODS: The clinical data of 82 cases who underwent endoscopic intestinal stenting in the First Affiliated Hospital of China Medical University for the treatment of left colon cancer and rectal cancer with intestinal obstruction from March 2014 to September 2018 were analyzed retrospectively. Treatments were defined as effective only if primary anastomosis was received without a stoma,and those clinical outcomes were analyzed by receiver operator characteristic(ROC)curve. Another 44 patients diagnosed with colorectal cancer complicated with intestinal obstruction underwent emergency surgery during the same period were the control group. The differences in the first-stage surgical anastomosis rate,average operation time,total hospitalization time,total hospitalization expenses,and postoperative complications between two groups were compared.RESULTS: The area under the ROC curve(AUC)was 0.693 with a certain degree of accuracy(P<0.05). Compared to those within 8 days,the rate of primary anastomosis was significantly higher in those received elective surgery over 8 days,the average operation time was significantly decreased,and the ICU utilization rate was also significantly decreased(P<0.05).Compared with the emergency operation group,the stent group had a significantly higher rate of primary anastomosis,and the average operation time was significantly lower. The postoperative ICU utilization rate and the incidence of diarrhea were significantly lower,but the total hospitalization days and total hospitalization expenses were significantly increased(P <0.05).CONCLUSION: Endoscopic intestinal stenting combined with elective surgery for left colon cancer and rectal cancer intestinal obstruction is safe and feasible,and elective surgery should be implemented over 8 days for its security.
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Objective·To investigate the relationship between the red blood cell distribution width (RDW) and the severity of right heart failure in patients with chronic obstructive pulmonary disease (COPD). Methods?·?A total of 265 patients with simple COPD and 268 COPD patients with right heart failure admitted to Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from October 2011 to September 2016 were enrolled. According to the New York Heart Association (NYHA) criteria, all COPD patients with right heart failure were divided into Group A (ClassⅠ), Group B (Class Ⅱ), Group C (Class Ⅲ) and Group D (Class Ⅳ). The RDW, mean corpuscular volume (MCV), pro-brain natriuretic peptide, and erythrocyte sedimentation rate were measured within 24 h after admission for all patients. The RDW trends and related influencing factors in different groups were analyzed and compared. Results?·?There was no significant difference in the gender, age, forced expiratory volume in one second (FEV1), and COPD exacerbation times between the COPD group and the COPD with right heart failure group (all P>0.05). However, there was a significant difference in red blood cell count (RBC), hemoglobin, MCV, RDW, pro-brain natriuretic peptide, and arterial partial pressure of oxygen (PaO2) (all P<0.05). In COPD with right heart failure group, there was no significant difference in age, RBC, hemoglobin, MCV, and PaO2among the four groups (all P>0.05). With the increase of the patients′ NYHA functional class, both pro-brain natriuretic peptide and RDW showed a similarly significant increase (both P=0.000). Through further multiple comparisons of RDW among four groups, there was a significant difference between any two groups (all P<0.05). Conclusion?·?RDW in patients with COPD with right heart failure is significantly elevated, and is closely related to right heart failure.
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Multidrug resistance (MDR) seriously affects the clinical efficacy of chemotherapeutic drugs. One of the main mechanisms of MDR is the overexpression of P-glycoprotein (P-gp) in tumor cells that reduces the intracellular drug concentrations and limits the effective use of chemotherapeutic drugs. Accordingly, application of P-gp inhibitors that can reverse tumor MDR is an effective strategy to enhance the anti-tumor effect of chemotherapeutic drugs. In recent years, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely applied as the potential P-gp inhibitor for its excellent P-gp inhibition effect as well as good safety. In this paper, we reviewed the P-gp inhibitors, the mechanisms of TPGS in reversing P-gp-mediated MDR and the application of TPGS-based nano-drug delivery system.
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<p><b>OBJECTIVE</b>To study the effects of embryonic lead exposure on food intake and bowel movement in offspring rats and possible mechanisms.</p><p><b>METHODS</b>Sprague-Dawley rats were given 0.1% (low-dose lead exposure group) or 0.2% (high-dose lead exposure group) lead acetate freely during pregnancy to establish an animal model of embryonic lead exposure. A blank control group was also established. The male offspring rats were enrolled in the study, and 10 male offspring rats from each group were selected to observe the changes in food intake, bowel movement, gastric emptying, intestine propulsion, and pathological inflammatory response in the gastric mucosa. Eight offspring rats were selected from each group, and electron microscopy and immunohistochemistry were used to observe the changes in the ultrastructure of jejunal microvilli and cell junction and the expression of cholecystokinin-8 (CCK-8) and motilin (MTL) in the feeding center, in order to reveal the possible mechanisms for abnormal gastrointestinal motility in offspring rats induced by embryonic lead exposure.</p><p><b>RESULTS</b>Compared with the control group, the low- and high-dose lead exposure groups had a significant reduction in daily food intake, a significant increase in water content of feces, a significant reduction in fecal pellet weight, and a significant increase in small intestine propulsion (P<0.05). The high-dose lead exposure group had a significant reduction in gastric emptying ability compared with the control group (P<0.05). Compared with the control group, the lead exposure groups had significantly greater pathological inflammatory changes in the gastric mucosa (P<0.05), significant reductions in the number and length of the jejunal microvilli and the number of epithelial desmosome junctions (P<0.05), a significant increase in the macula densa gap (P<0.05), and significant increases in the expression of MTL and CCK-8 in the feeding center (P<0.05), in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>The degree of gastrointestinal structural injury and expression levels of MTL and CCK-8 in the feeding center are lead dose-dependent, which may be important mechanisms for changes in food intake, bowel movement, and digestive functions in offspring rats induced by embryonic lead exposure.</p>
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Animales , Femenino , Ratas , Defecación , Ingestión de Alimentos , Feto , Vaciamiento Gástrico , Yeyuno , Patología , Plomo , Toxicidad , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To explore the effects of embryonic lead exposure on motor function and balance ability in offspring rats and the possible mechanisms.</p><p><b>METHODS</b>An animal model of embryonic lead exposure was prepared with the use of pregnant Sprague-Dawley rats freely drinking 0.1% (low-dose group, LG) or 0.2% (high-dose group, HG) lead acetate solution. A normal control group (NG) was also set. The male offspring rats of these pregnant rats were included in the study, consisting of 12 rats in the NG group, 10 rats in the LG group, and 9 rats in the HG group. The offspring rats' motor function and balance ability were evaluated using body turning test and coat hanger test. Eight rats were randomly selected from each group, and immunohistochemistry and Timm's staining were employed to measure the expression of c-Fos and mossy fiber sprouting (MFS) in the hippocampus.</p><p><b>RESULTS</b>The HG group had a significantly longer body turning time than the NG and LG groups (P<0.05), and the LG group had a significantly longer body turning time than the NG group (P<0.05). The HG group had a significantly lower score of balance ability than the NG and LG groups (P<0.05), and the LG group had a significantly lower score of balance ability than the NG group (P<0.05). The area percentage of c-Fos-positive neurons in the hippocampal CA1 region was significantly higher in the HG group than in the other two groups (P<0.05), and it was significantly higher in the LG group than in the NG group (P<0.05). The semi-quantitative scores of MFS in the hippocampal CA3 region and dentate gyrus were significantly higher in the HG group than in the other two groups (P<0.05), and they were significantly higher in the LG group than in the NG group (P<0.05).</p><p><b>CONCLUSIONS</b>Embryonic lead exposure could impair the offspring rats' motor function and balance ability. These changes may be related to increased c-Fos expression in the hippocampal CA3 region and abnormal MFS in the hippocampal CA3 region and dentate gyrus.</p>
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Animales , Femenino , Masculino , Embarazo , Ratas , Feto , Hipocampo , Química , Plomo , Toxicidad , Fibras Musgosas del Hipocampo , Actividad Motora , Equilibrio Postural , Proteínas Proto-Oncogénicas c-fos , Ratas Sprague-DawleyRESUMEN
The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio (TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.